A high-resolution map of active promoters in the human genome

A high-resolution map of active promoters in the human genome
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DOI:
10.1038/nature03877
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发表时间:
2005-08-11
期刊:
影响因子:
64.8
通讯作者:
Ren, B
Ren, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim, TH;Barrera, LO;Ren, B

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在真核细胞中,每个蛋白质编码基因的转录始于启动子上RNA聚合酶II前起始复合物(PIC)的组装(1)。启动子与增强子、沉默子和绝缘子一起定义了指定基因表达模式的组合代码(2)。我们分析人类基因组中编码的控制逻辑的能力目前受到缺乏关于大多数基因启动子的准确信息的限制(3)。在这里,我们描述了一个全基因组的地图,在人类成纤维细胞的活性启动子,通过实验定位的PIC结合位点在整个人类基因组。该图谱定义了对应于6,763个已知基因的10,567个活性启动子和至少1,196个未注释的转录单位。图谱的特征表明人类基因广泛使用多个启动子,基因组中活性启动子广泛聚集。此外,全基因组表达谱的检查揭示了四种定义细胞转录组的启动子。这些结果提供了一个全球性的看法,在人类细胞中的转录机制,染色质结构和基因表达之间的功能关系。
In eukaryotic cells, transcription of every protein-coding gene begins with the assembly of an RNA polymerase II preinitiation complex (PIC) on the promoter(1). The promoters, in conjunction with enhancers, silencers and insulators, define the combinatorial codes that specify gene expression patterns(2). Our ability to analyse the control logic encoded in the human genome is currently limited by a lack of accurate information regarding the promoters for most genes(3). Here we describe a genome-wide map of active promoters in human fibroblast cells, determined by experimentally locating the sites of PIC binding throughout the human genome. This map defines 10,567 active promoters corresponding to 6,763 known genes and at least 1,196 un-annotated transcriptional units. Features of the map suggest extensive use of multiple promoters by the human genes and widespread clustering of active promoters in the genome. In addition, examination of the genome-wide expression profile reveals four general classes of promoters that define the transcriptome of the cell. These results provide a global view of the functional relationships among transcriptional machinery, chromatin structure and gene expression in human cells.